E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
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MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 9.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10028228 |
E.1.2 | Term | Multiple myeloma |
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E.1.3 | Condition being studied is a rare disease | Yes |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
The primary objective is to evaluate the clinical activity, measured by M-protein serum and urine levels, of two different dose regimens (0.2 mg/kg, leading to an intermittent saturation of NK receptors and 2mg/kg leading to a sustained saturation of NK receptors) of IPH2101 administered as a single agent in multiple myeloma patients who achieved, after the completion of any first line treatment, including conventional or high dose chemotherapies, a partial or very good partial response (PR or VGPR), stable for at least 2 months. |
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E.2.2 | Secondary objectives of the trial |
The secondary objectives are: o To confirm the safety profile of the dose and administration schedules of IPH2101 in this population; o To assess PK of two different dose regimens of IPH2101 o To evaluate the biological activity of IPH2101 on: - KIR occupancy - NK cell phenotype - NK cell function - Cytokine release o To confirm the absence of immunogenicity of IPH2101 o To document per study and post study efficacy parameters until 2 years after the end of study : - Overall Survival (OS) - Duration of response (DOR) - Progression free Survival (PFS) and Time to Progression (TTP)
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1) MM which initially required a systemic therapy and received a first line treatment, conventional doses of chemotherapies or high dose chemotherapy and an autologous transplantation of hematopoietic cells, followed or not by a consolidation treatment. 2) Residual disease considered as evaluable with: - Quantifiable serum M-protein 3) Responses which are partial (PR and VGPR) and in plateau - Partial response should meet the IMWG uniform response criteria: a ≥ 50% reduction from value of serum M-protein before the first line chemotherapy treatment and a reduction in 24h urinary M protein by ≥ 90% or to < 200 mg / 24h; - Very good partial response according to the IMWG uniform response criteria with 90% or greater reduction in serum M-protein plus urine M-protein level < 100 mg/24h; Furthermore the M protein should spike in the gamma globulin area; - Plateau phase is defined by stable levels of M protein in serum checked 4 weeks apart on at least 3 consecutive samples. Fluctuations ± 1 week in sampling and ± 5 % in M protein levels are allowed. 4) ECOG performance status of 0, 1 or 2 5) Clinical laboratory values at screening: - Calculated creatinine clearance (according to MDRD) > 50 ml/min - Platelet > 50 x 109 /l - ANC > 1 x 109 /l - Bilirubin levels < 1.5 ULN ; ALT and AST < 2.5 ULN (grade 1 NCI) 6) Male or female patient who accepts and is able to use recognised effective contraception (oral contraceptives, IUCD, barrier method of contraception in conjunction with spermicidal jelly) throughout the study. 7) Signed inform consent obtained before any trial-related activities |
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E.4 | Principal exclusion criteria |
1) Age < 18 years old or > 75 years old 2) Previous consolidation/ maintenance therapy by Imid (thalidomide, lenalidomid) or bortezomib within the last 2 months 3) Treatment with chemotherapy, systemic corticosteroid within the previous 2 months 4) Treatment with growth factors (EPO, G- or GM-CSF) within the previous 1 month 5) MM in VGPR with a monoclonal spike in the beta globulin area 6) Radiotherapy for bone or visceral lesion within the last 3 months 7) Use of any investigational agent within the last 2 months 8) Primary or associated amyloidosis 9) Peripheral neuropathy of grade ≥ III according to the CTCAE of the NCI 10) Abnormal cardiac status with any of the following a) NYHA stage III or IV congestive heart failure b) myocardial infarction within the previous 6 months c) symptomatic cardiac arrhythmia despite treatment 11) Current active infectious disease or positive serology for HIV, HCV or positive Hbs Antigen 12) History of or current auto-immune disease 13) Serious concurrent uncontrolled medical disorder 14) History of other malignancy (apart from basal cell carcinoma of the skin, or in situ cervix carcinoma) 15) History of allogenic hematopoietic cell or solid organ transplantation 16) Pregnant or lactating women 17) Any medical condition which is regarded by the investigator as incompatible with the study participation 18) Any psychological, familial, sociological or geographical condition potentially hampering compliance with the study protocol and follow-up schedule |
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E.5 End points |
E.5.1 | Primary end point(s) |
M Protein will be measured in serum and urine: o At Screening o Every 4 weeks during the study period from V1-day1 to End of Study Post study follow up: then every 3 months during 2 years according to standard practices The primary end point will be the rate of patients achieving a response based on M- Protein levels in serum and urine sustained for at least one month. Response will be defined: o In patients with a serum M-protein > 5 g/l, as a reduction of at least 25% (minor response according to EBMT Appendix VI) from baseline of serum M-protein confirmed on two consecutive determinations at 4 weeks interval; o In patients with a serum M-protein ≤ 5 g/l, as a negative electrophoresis In any case, a reduction ≥ 50% or a reduction to < 200mg/ 24h in 24h urine M-protein is required.
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | No |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | Yes |
E.6.7 | Pharmacodynamic | Yes |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | No |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | Yes |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | Yes |
E.8.1.1 | Randomised | Yes |
E.8.1.2 | Open | Yes |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | No |
E.8.1.5 | Parallel group | No |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | No |
E.8.2.2 | Placebo | No |
E.8.2.3 | Other | Information not present in EudraCT |
E.8.3 |
The trial involves single site in the Member State concerned
| No |
E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
E.8.4.1 | Number of sites anticipated in Member State concerned | 12 |
E.8.5 | The trial involves multiple Member States | No |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | No |
E.8.6.2 | Trial being conducted completely outside of the EEA | Information not present in EudraCT |
E.8.7 | Trial has a data monitoring committee | Yes |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 1 |
E.8.9.1 | In the Member State concerned months | 6 |
E.8.9.1 | In the Member State concerned days | |